Description:

The goal of this study is to determine the biochemical mechanisms responsible for TBT induced imposex and examine the interrelationship between TBT and other environmental xenobiotics in the development of these sexual abnormalities. The following objectives will be addressed in this study: 1) investigate the biochemical and/or molecular mechanisms by which TBT alters the regulation of steroid hormones and neurohormones to induce imposex in marine mollusks; 2) determine the effects of other environmental contaminants on TBT's ability to induce imposex; and 3) determine whether the mechanisms identified in laboratory studies on imposex plays a significant role in field-induced organisms.

Approach:

The first objective of this study will be to assess the overall effect of TBT exposure on hormone biosynthesis. The hormone substrates, each of which are metabolized by a cytochrome P450-mediated reaction, will include cholesterol, progesterone, androstenedione and testosterone. The functioning of these biochemical and/or molecular mechanisms will be compared to those from organisms exposed to a mixture of environmental endocrine-disrupting chemicals, specifically TBT and 3-methylcholanthrene (3-MC). Control of hormone biosynthesis will also be examined by investigating the effect of TBT and TBT plus 3-MC on the production of neurohormones, i.e. the penis-morphogenic factor or the egg-laying hormone. These neurohormones are ultimately responsible for sexual differentiation and reproduction in mollusks. We wil also investigate the ability of snails exposed to 3-MC to detoxify TBT via debutylation to DBT thereby decreasing their risk of exposure to toxic concentrations of TBT. Finally, snails will be transferred from a clean site to contaminated environments where the native population is known to experience a high degree of imposex. The mechanisms differentiated in earlier studies will be utilized to examine the induction of imposex in field exposed organisms.

Expected Results:

It is expected that results from this research program will provide explanations for the environmental androgenization of female gastropods. The mechanisms of action for hormone modulation are not expected to be simplistic in nature. Rather, the interaction between an androgenizing compound, TBT, and an anti-androgenizing compound, a PAH, commonly found in field-exposed organisms is expected to involve more than one portion of the hormone biosynthetic pathway. The data collected from this study will provide mechanistic explanations for the interference of sexual differentiation by endocrine-disrupting compounds.

Improvement in Risk Assessment or Risk Management: By determining the interrelationship between environmental androgens and anti-androgen/estrogen-like compounds this study will provide valuable data linking the exposure of organisms to biological effects. Because of the critical roles that sexual development and reproduction have on populations, this information is of great interest. Therefore, our results will provide valuable information to state and federal agencies regarding their mission of species management and ecological/biological risk assessment.

Progress and Final Reports:

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.